This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Group A streptococci (GAS) cause a wide spectrum of diseases and certain GAS M protein sequence types (emm types) have been associated with such sequelae as acute rheumatic fever (ARF). While the incidence of ARF has declined in industrialized countries, it remains high in Hawaii particularly among Samoans. The objectives of the proposed research are to identify GAS types responsible for clinical disease, particularly ARF in Samoans, and to determine the serologic responses to these specific infections. Our central hypothesis is that the GAS emm types associated with sequelae in Samoans in Hawaii originate from circular migration of Samoans, thus resulting in the high incidence of ARF in Hawaii. The secondary hypothesis is that the antibody responses to GAS infections are different in Samoans. We base these hypotheses on our preliminary studies which indicate that GAS emm types, which are uncommonly found on the continental US and not classically associated with ARF, are frequently identified among Hawaiian patients with GAS infections and ARF;and that asymptomatic children and ARF patients of Samoan ethnicity have higher prevalence rates of GAS infections due to these uncommon emm types. The proposed study will address these specific aims: Specific aim 1. Determine the GAS types circulating among Samoan children in Hawaii and American Samoa: a. Prospectively collect GAS isolates from throats of asymptomatic school-aged children, patients with mild throat and skin infections, patients with invasive infections and with ARF in American Samoa and Hawaii, b. Perform emm gene sequencing, T agglutination typing, opacity factor typing of these GAS isolates, c. Analyze the differences among GAS emm types isolated in American Samoa and Hawaii. Specific aim 2. Determine the GAS types and anti-streptococcal antibody responses in cohorts of Samoans: a. Establish two cohorts of 50 Samoan children each from Hawaii and American Samoa to include patients with ARF, pharyngitis, skin infection, invasive GAS infection and asymptomatic school-aged children with GAS colonization and repeat throat swabs of these cohorts 3 times within an 18-month study period, b. Prospectively determine the anti-streptococcal antibody responses [antistreptolysin O and anti-DNase B titers] in the two cohorts. The study results will provide new knowledge about GAS epidemiology associated with human migration and will yield comprehensive data to address the means by which different populations are affected differently by a wide variety of GAS types. Also, these studies will provide much-needed information about the transmission dynamics of GAS and exert an impact on tailoring candidate GAS vaccines for these vulnerable populations.